The Molecular Wire Approach to Sensory Signal Amplification

Abstract

A chemosensor is a molecular device designed to detect a specific molecule or class of molecules.1a,b Research in this field is poised for considerable advances in the coming years with the advent of diverse methods for analyte detection and new developments in the field of molecular recognition. To date, the most common signal transduction schemes utilize optical or electrical methods.1c Fluorescence is a highly sensitive optical transduction method, and analyte binding events that produce an attenuation, enhancement, or wavelength shift in the emission can be used to produce a functional sensor.1d Changes in absorption spectra, while less sensitive, have also been extensively used.1e Redox processes are widely used in electrical-based transduction methods, and typical systems function in either potentiometric or amperometric modes.1f Conductometric detection schemes based on SnO2, conducting polymers,1h and phthalocyanines1i have also been investigated. As shown in Scheme 1, a chemosensor is composed of two functional elements, a receptor and a reporter group, which need not be separate in identity. When the equilibrium between the analyte and receptor is rapid, sensors can be produced that provide a real-time response, which continuously varies with the concentration of the analyte. The detection sensitivity is determined by both the ability to measure the transduction event and the association constant of the receptor-analyte complex. As a result, when pursuing higher sensitivity one may seek instrumentation improvements and/or endeavor to increase the magnitude of the association constant of the receptor-analyte complex. The standard approach to higher association constants is to design highly preorganized receptors that do not pay a high entropic penalty for complexation. The downside of this approach is that preorganization and high association constants generally result in slow dissociation kinetics. A molecular chemosensor with slow kinetics or an irreversible response cannot yield a reversible real-time response. Molecular systems displaying irreversible or slow behavior are nonetheless useful, but are properly called dosimeters or indicators. Methods may be developed to allow irreversible systems to function in a sensory device. For example, the device can be “reset” by chemical, electrochemical, photochemical, or physical events. These processes can cause the analyte to dissociate from the receptor or can result in the replacement of the indicator (chemosensor) molecules. Such approaches have the disadvantage of introducing additional complexity into the sensor devices. This Account describes an approach to enhancing the sensitivity of chemosensors in effect by “wiring chemosensory molecules in series” (Scheme 2). Recent work from my research laboratory has shown that this molecular wire approach provides a universal method by which to obtain signal amplification relative to single molecule systems. I will use the term molecular wire interchangeably with conducting polymer. For the sake of clarity, some representative conducting polymers are shown in Scheme 3. These materials are insulators in their neutral (undoped) Timothy M. Swager is a native of Montana and received a B.S. from Montana State University in 1983 and a Ph.D. from the California Institute of Technology in 1988. After a postdoctoral fellowship at the Massachusetts Institute of Technology (1988-1990), he began his independent academic career at The University of Pennsylvania and was promoted to Professor in 1996. He is currently a Professor of Chemistry at the Massachusetts Institute of Technology. His interests in supramolecular chemistry include the design of electronic polymers, sensors, and liquid crystals, molecular recognition, and catalysis. Scheme 1